Drug could improve outcomes for children with high-risk leukemia

Results from a new study could benefit some children with high-risk acute myeloid leukemia (AML). A therapeutic regimen that combined the drug gemtuzumab ozogamicin (GO) with conventional three-drug chemotherapy was associated with improved survival in children with AML who underwent bone marrow transplantation.

Acute myeloid leukemia is diagnosed in approximately 500 children annually in the United States, accounting for about 20% of childhood leukemia cases. Bone marrow transplantation is the best therapeutic option for pediatric patients with AML who have suitable bone marrow donors, and survival rates are highest for patients who lack detectable cancer cells before transplantation.

In the current study, combination therapy with GO plus standard chemotherapy with cytarabine, daunorubicin, and etoposide helped eliminate minimal residual disease (MRD) in children with AML who initially responded poorly to chemotherapy. The overall 5-year survival of patients who received combination therapy was 55%, compared with 36% for patients with similar MRD who received standard chemotherapy alone.

Although the difference in survival was not statistically significant, GO probably contributed to improved outcomes for these patients by decreasing MRD prior to transplantation, said lead researchers from St. Jude Children's Research Hospital in Memphis, Tennessee. The study appeared in the November 15 issue of Cancer (2013; doi:10.1002/cncr.2833).

Gemtuzumab ozogamicin received accelerated approval from the US Food and Drug Administration in 2000 for treatment of AML in adults. However, concerns about safety and efficacy led to voluntary withdrawal of the drug in 2010. Several studies performed when the drug was available have reported promising results in adults with AML. These reports prompted the analysis of data from pediatric AML patients who received GO in a clinical trial conducted while the drug was available. Treatment with GO was not associated with severe toxicity in this or other recent studies.

The drug was designed to be more selective than traditional chemotherapy agents, which kill both malignant and healthy rapidly dividing cells. Gemtuzumab ozogamicin targets a protein expressed on the surface of about 90% of AML cells. The results of this and other recent studies suggest that adults and children with AML may benefit from treatments based on a similar mechanism to GO, researchers said. Work has begun on new approaches such as antibody-based therapies targeting the same AML surface protein, said the study's senior author, Jeffrey Rubnitz, MD, PhD, of the St. Jude Department of Oncology.

"Currently there are few options for AML patients who relapse or do not respond to conventional therapy," said first author Carol O'Hear, MD, PhD, a St. Jude postdoctoral oncology fellow.

Added Rubnitz: "Without new agents, it is unlikely we will be able to improve pediatric AML survival beyond current levels of about 70%. The results of this and earlier studies make a strong case that some patients benefit from this targeted therapy, which has us looking for new ways to take aim at the same protein."